sFRP1 has a biphasic effect on doxorubicin-induced cardiotoxicity in a cellular location-dependent manner in NRCMs and Rats.

sFRP1 has a biphasic effect on doxorubicin-induced cardiotoxicity in a cellular location-dependent manner in NRCMs and Rats. Arch Toxicol. 2018 Oct 30;: Authors: Hu Y, Guo Z, Lu J, Wang P, Sun S, Zhang Y, Li J, Zheng Q, Guo K, Wang J, Jiang J, Liu P Abstract Doxorubicin (Dox) is an effective anticancer drug, however, its clinical application is restricted by the life-threatening cardiotoxic effects. Secreted Frizzled-related protein 1 (sFRP1) has been reported to participate in both the cancer and cardiovascular diseases and was one of the differential expression genes in normal hearts compared with Dox-treated hearts. Thus, it is important to reveal the potential role of sFRP1 in Dox-induced cardiotoxicity. Here, we show that sFRP1 has a biphasic effect on Dox-induced cardiotoxicity in a location-dependent manner. The secretion of sFRP1 was significantly increased in Dox-treated neonatal rat cardiomyocytes (NRCMs) (1 µM) and SD rats (5 mg/kg/injection at day 1, 5, and 9, i.p.). Adding the anti-sFRP1 antibody (0.5 µg/ml) and inhibiting sFRP1 secretion by caffeine (5 mM) both relieved Dox-induced cardiotoxicity through activating Wnt/β-catenin signaling, whereas increasing the secretion of sFRP1 by heparin (100 µg/ml) had the opposite effect. The intracellular level of sFRP1 was significantly decreased after Dox treatment both in vitro and in vivo. Knockdown of sFRP1 by sgRNA aggravated Dox-induced cardiotoxicity, while moder...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research